Cocaine remains a popular illicit drug, and maternal use of cocaine during pregnancy has been associated with increased risk of preterm delivery, intrauterine growth retardation, urinary tract anomalies and cerebral malformations. In addition, a number of studies have suggested a causal relationship between maternal cocaine use and the development of necrotizing enterocolitis (NEC) in their infants. Cocaine administration is known to elevate circulating catecholamine levels, the effects of which are mediated through adrenergic receptors. Multiple subtypes of alpha adrenergic receptors have been identified through molecular cloning, but their precise physiologic relevance has yet to be elucidated. To determine the role of different subtypes of alpha-2 adrenergic receptors in the pathogenesis of neonatal NEC after maternal administration of cocaine, we studied the intestines of postnatal day 0 rats after in utero exposure to cocaine.

Timed-pregnant rats were treated with daily injections of cocaine or saline from embryonic day 8 through embryonic day 20. The newborn animals were sacrificed on the day of birth and the intestines were preserved in situ. The expression of alpha-2C10 and alpha-2C4 adrenergic receptor mRNAs was studied using in situ hybridization with oligonucleotide probes specific for each of the receptor subtypes. Quantitative densitometric analysis was performed using NIH IMAGE. Both subtypes were expressed in the neonatal intestine with more intense expression of the alpha-2C10 receptor subtype. Alpha-2C10 receptor mRNA was reduced in the cocaine exposed animals to 94% of control while the alpha-2C4 adrenergic receptor mRNA was decreased in the cocaine exposed animals to 78% of control. These differences were both statistically significant.

There is a post-norepinephrine induced hyperemia in the rat mesenteric circulation which has been shown to be modulated by alpha-2 adrenergic receptors. These data suggest that down-regulation of alpha-2 adrenergic receptors in the newborn after maternal cocaine administration may cause alterations in vascular responses to hypoxia or hypotension, thus increasing the risk for neonatal NEC.